Development of a 3D Human cell-based ulcer model to investigate anti-leishmanial nano-based drug therapies

P SCHILRREFF; C ZOSCHKE; MJ MORILLA; EL ROMERO; M SCHÄFER-KORTING

Leipzig

Encuentro; Network Meeting of the Alexander von Humboldt Foundation; 2019

Leishmaniasis is endemic in 88 countries of which 72 are developing countries (figure 1) [1]. Associated with poverty, annually around 1.5-2 million children and adults develop symptomatic disease in which cutaneous leishmaniasis (CL) forms embrace 1-1.5 million of the total new cases. Leishmania parasite is transmitted by mosquito bites and macrophages are the final host cells [2]. A hallmark of CL is the development of papules or nodules followed by ulceration at the site of infection. CL, while not fatal, produces long-lasting especially devastating and disfiguring ulcers. The notion that the immune system and not the parasite per se causes tissue damage is supported by a recent study in mice [3]. The immaturity of the infant´s immune system and the absence of prior immunity are potential contributors to the high rates of infection among infants and young children [2].Unfortunately, existing treatments have low efficacy, life-threatening side effects / high toxicity, and can result in parasite resistance, too. The development of more effective therapies has been hampered by the lack of predictive in vitro methods. To address the need for a realistic model of CL related ulcer, a 3D disease model is proposed as a biologically relevant and predictive experimental platform for the discovery of more effective topical strategies in ulcer healing.